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Updated: Dec 26, 2025
Oral Administration of Rotenone using a Gavage and Image Analysis of Alpha-synuclein Inclusions in the Enteric Nervous System
Published on: October 26, 2010
Protective effect of metformin against rotenone-induced parkinsonism in mice
Dong-Xin Wang1, An-Di Chen2, Qing-Jun Wang2,3
1Institute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
Abstract:
Rotenone is a mitochondrial complex I inhibitor, which can cause the death of dopaminergic (DA) neurons and Parkinson's disease (PD). Currently, whether metformin has a protective effect on neurotoxicity induced by rotenone is unclear. The purpose of this study was to evaluate the potential protective effect of metformin against rotenone-induced neurotoxicity. PD animal model was established by unilateral rotenone injection into the right substantia nigra (SN) of C57BL/6 mice. The behavioral tests were performed by rotarod test and cylinder test. The numbers of TH-positive neurons and Iba-1 positive microglia in the SN were investigated by immunohistochemical staining. The mRNA levels of proinflammatory cytokines (TNF-α and IL-1β) and molecules involved in endoplasmic reticulum (ER) stress (ATF4, ATF6, XBP1, Grp78, and CHOP) in the midbrain were detected by Quantitative real-time PCR. This study showed that 50 mg/kg metformin given orally daily, beginning 3 d before rotenone injection and continuing for 4 weeks following rotenone injection, significantly ameliorated dyskinesia, increased the number of TH-positive neurons, and mitigated the activation of microglia in the SN in rotenone-induced PD mice. Furthermore, 50 mg/kg metformin markedly downregulated the expression of proinflammatory cytokines (TNF-α and IL-1β) and ER stress-related genes (ATF4, ATF6, XBP1, Grp78, and CHOP) in rotenone-induced PD mice. Metformin has a protective effect on DA neurons against rotenone-induced neurotoxicity through inhibiting neuroinflammation and ER stress in PD mouse model.
Insights
Metformin protects against rotenone-induced neurotoxicity in a Parkinson's disease mouse model. It reduces inflammation and endoplasmic reticulum stress, preserving dopaminergic neurons and improving motor function.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Rotenone, a mitochondrial complex I inhibitor, induces dopaminergic neuron death, mimicking Parkinson's disease (PD).
- The neuroprotective potential of metformin against rotenone-induced neurotoxicity remains largely uncharacterized.
Purpose of the Study:
- To investigate the protective effects of metformin against rotenone-induced neurotoxicity in a mouse model of Parkinson's disease.
Main Methods:
- A Parkinson's disease mouse model was established using unilateral rotenone injection into the substantia nigra (SN).
- Mice were treated with metformin (50 mg/kg daily) starting 3 days before rotenone injection and continuing for 4 weeks.
- Behavioral tests (rotarod, cylinder), immunohistochemistry (TH-positive neurons, Iba-1 microglia), and quantitative real-time PCR (cytokines, ER stress markers) were employed.
Main Results:
- Metformin treatment significantly improved motor deficits (dyskinesia) in rotenone-induced PD mice.
- Metformin increased the survival of tyrosine hydroxylase (TH)-positive dopaminergic neurons and reduced microglial activation in the SN.
- Metformin downregulated mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β) and endoplasmic reticulum (ER) stress markers (ATF4, ATF6, XBP1, Grp78, CHOP).
Conclusions:
- Metformin demonstrates significant neuroprotective effects against rotenone-induced neurotoxicity in a PD mouse model.
- These protective effects are mediated by the inhibition of neuroinflammation and endoplasmic reticulum stress pathways.
- Metformin holds potential as a therapeutic agent for Parkinson's disease by safeguarding dopaminergic neurons.
